Darier's disease (keratosis follicularis)

Question 1

Darier’s disease is inherited in _____ fashion with _____ penetrance and ____ expressivity.

Answer 1

Autosomal Dominant (darier is dominant)

• complete penetrence
• variable expressivity

Question 2

Peak ago of onset in Darier’s disease?

Answer 2

puberty

Question 3

What is the prognosis of Darier’s disease?

Answer 3

• chronic course without remission

Question 4

What is the mutation in Darier’s disease?

Answer 4

• ATP2A2 (which encdoes SERCA2)

Question 5

Darier’s disease mutation is ATP2A2, what is the pathogenesis of the disease with relation to this mutation?

Answer 5

• remember fingers, 2 A 2 (the V that your fingers form reminds you of V-knicking of fingernails)
• ATP2A2 encodes SERCA2= calcium ATPase of endoplasmic reticulum–>defective calcium in ER–>impaired synthesis and folding of cell adhesion proteins—> keratinocyte acantholysis and apoptosis

Question 6

What are the primary lesions of Darier’s disease?

Answer 6

• Malodorous, warty, crusted, and red-brown papules/plaques in seborrheic distribution.
• almost always see keratotic palmar papules/pits; longitudinal red and white alternating nail streaks w distal V-shaped notching (50% have oral cobblestoning)

Question 7

What are some classic findings in Darier’s disease (apart from the primary warty crusted red-brown papules/plaques in seborrheic distribution)?

Answer 7

ALMOST ALWAYS: keratotic palmar papules/pits; longitudinal red and white alternating nail streaks w distal V-shaped notching (50% have oral cobblestoning)

Question 8

Type I segmental Darier’s disease presents in _____ distribution.

Answer 8

• blaschkoid strekas of Darier’s lesions

Question 9

Type 2 segmental Darier’s disease distribution of lesions:

Answer 9

• Generalized w/ focal areas of severe involvement

Question 10

Darier’s disease patients are prone to secondary infections, one of the most concerning is _______

• What other blistering disease do you worry about this in?

Answer 10

• Eczema herpeticum (aka kaposi’s varicelliform eruption)

- Hailey Hailey

Question 11

What are some comorbidities a/w Darier’s disease?

Answer 11

• increased incidence of epilepsy, intellectual impairment, bipolar disorder, and depression
• (all stuff wrong in the brain)

Question 12

Histopathology of Darier’s disease:

Answer 12

• Papillomatous epidermal hyperplasia w/ epidermal acantholysis and dyskeratosis (core ronds and core grains)

Question 13

What layers do you see Corps ronds and corps grains in Darier’s disease?

Answer 13

• Corps ronds in the spinous layer mostly
• Corps grains in the corneal layer (these are just the corps ronds getting flattened as the ascend)

Question 14

Treatment of Darier’s disease?

Answer 14

• systemic retinoids (>90% effective)
• topical CS and retinoids, topical antimicrobials to decrease odor